Targeting VEGFRi resistance through HIF-1á suppression: Phase II clinical trial evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent platinum resistant ovarian cancer.

TPS5614 Background: Ovarian cancer (Ov.Ca.) is the leading cause of death among gyn malignancies. Limited treatment options exist for women whose tumors have become platinum resistant. Hypoxia Inducible Factor-1α (HIF-1α) is a master regulator of key cancer cell survival pathways and facilitates resistance to anti-angiogenic therapies. CRLX101, a novel nanoparticle-drug conjugate that differentially delivers camptothecin into cancer cells, durably suppresses HIF-1α and the combination of CRLX101 with anti-angiogenic drugs incl. bevacizumab (Avastin, Genentech/Roche)(BEV) achieves notable drug-drug synergy in pre-clinical models. Phase 2 monotherapy results achieved with CRLX101 and presented at ASCO 2014 exceeded expectations in this setting and established the basis for this follow-on study. Methods: This phase 2 open label, two-stage clinical trial evaluates the combination of CRLX101 plus BEV in pts. with epithelial ovarian, tubal or primary peritoneal cancer progressing through prior platinum-containi...